Corneal Antigen-Presenting Cells

Abstract

Corneal antigen-presenting cells (APCs) were thought to reside exclusively in the peripheral cornea. However, recent evidence demonstrates that the central cornea is also endowed with a heterogeneous population of bone marrow-derived cells, including epithelial Langerhans cells (LCs) and anterior stromal dendritic cells (DCs), which under certain conditions can function as APCs. While the corneal periphery contains mature and immature resident bone marrow-derived DCs, the central cornea is endowed exclusively with highly immature/precursor-type DCs. During inflammation, a majority of resident DCs undergo maturation by acquiring high expression of major histocompatibility complex class II antigens and B7 (CD80/CD86) and CD40 costimulatory molecules. Further, macrophages are present in the posterior corneal stroma. In transplantation, donor-derived DCs migrate to host cervical lymph nodes and activate host T cells via the direct pathway when allografts are placed in inflamed, but not normal uninflamed, host beds. Migration of DCs to cervical lymph nodes is, in part, regulated by the vascular endothelial growth factor receptor-3 (VEGFR-3) that is expressed on corneal DCs. Blockade of the VEGFR-3 signaling significantly suppresses corneal DC trafficking to draining lymph nodes and rejection of corneal transplants. Much remains unknown about the function of these cells including their role in innate responses as well as in tolerance. Regardless, these data revise the tenet that the cornea is immune privileged due to a lack of resident lymphoreticular cells per se, but suggest that the cornea is capable of actively participating in the immune response to foreign antigens and autoantigens, rather than being a passive bystander. Additionally, one important aspect of immune privilege is likely the ocular 'imposition' of the immature phenotype on its resident bone marrow-derived cells.